Reagent strips are quite popular for use in colorimetric reactions, in which strip color is read by a hand-held meter, specifically, reagent strips are useful in the determination of analyte levels in blood. Even more specifically, reagent strips have been useful in the determination of glucose levels in whole blood. Blood samples are placed on the reagent strip, and after reaction with components embedded in the strips, a determination of glucose levels in whole blood is made. The meter is capable of discerning information from the reaction to determine glucose levels in whole blood. Measuring meters, such as glucose measuring meters, and reagent strips, such as glucose measuring reagent strips, vary in accuracy and preciseness of measuring capabilities. It is therefore necessary to provide a monitoring agent, known as a control solution, which determines whether meters and strips are rendering meaningful descriptions of glucose levels. Of course, it is important to have this solution act in as close as possible a manner to the sample, i.e., whole blood.
In porous membrane-based reagent strips, red blood cells (erythrocytes) play an important part in controlling sample flow. When whole blood is applied to the top surface of the membrane, the liquid portion of the blood (plasma) immediately penetrates the porous structure, drawn in by capillary action. As plasma is drawn toward the surface of the membrane, it carries erythrocytes with it. When the erythrocytes contact the surface of the membrane, they are prevented from entering the membrane by pores which are smaller than the erythrocytes. The erythrocytes may rupture due to surface properties of the membrane or capillary suction, releasing their liquid contents into the membrane, but the erythrocyte cell membrane (ruptured or not) remains at the reagent membrane surface, blocking progress of plasma into the pores. When all of the surface pores are covered by erythrocytes, all flow of plasma into the reagent membrane ceases.
This flow control feature of whole blood is important for three reasons. First, if flow of plasma were to continue unimpeded, gravity would cause excess fluid to accumulate on the lower surface of the membrane where reading takes place. This excess fluid would impede accurate reflectance measurements of developed color on the reading surface. Second, continued delivery of analyte (i.e., glucose in the case of a glucose reagent strip) to the reagent system results in increasing color intensity as long as flow continues. In contrast, if plasma flow is stopped upon reaching the reading surface of the membrane, then the analyte sample size is controlled, and color variation ceases when this analyte is completely reacted. Third, in the absence of a flow controlling factor, plasma will be drawn into the membrane surrounding the sample application zone, carrying with it reagents and developed dyes, and depleting the concentration of these chemicals in the center of the zone.
Separately or in combination, the above three effects inhibit the ability of the system to reproducibly measure analyte levels in aqueous solutions. Thus, when analyte is presented in an artificial matrix (control solution), better precision is obtained if this artificial matrix possesses flow control characteristics similar to whole blood. Precision is important with control solution because typically the reagent strip/meter system is said to be functioning properly if the control solution produces a reading in a prescribed range. As the imprecision of the system increases, this range must be broadened, and the value of a single control test as an indication of system performance decreases.
Previous control solutions have attempted to mimic whole blood samples on reagent strips, but for reasons listed below, control solution reproducibility is difficult to attain. Current control solutions are made viscous by the addition of water-soluble polymers such as methyl cellulose, polyvinylpyrrolidone or hydroxypropyl cellulose. This increased viscosity greatly slows down, but does not completely eliminate the formation of excess solution on the reading surface. Thus, a viscosity-modified control solution give&gt;better precision than an unmodified aqueous control, but does not operate as well as blood. In addition, the high viscosity necessary to significantly slow the flow makes the control solution difficult to handle during manufacture and dispensing.